Cited by 362Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsHypothalamic control of reproductive hormones

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Long or Highly Irregular Menstrual Cycles as a Marker for Risk of Type 2 Diabetes Mellitus

Solomon, Caren G.·2001·JAMA

DOI 10.1001/jama.286.19.2421

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Abstract

CONTEXT: Although oligomenorrhea has been associated cross-sectionally with insulin resistance and glucose intolerance, it is not known whether oligomenorrhea is a marker for increased future risk of type 2 diabetes mellitus (DM). OBJECTIVE: To prospectively assess risk of type 2 DM in women with a history of long or highly irregular menstrual cycles. DESIGN AND SETTING: The Nurses' Health Study II, a prospective observational cohort study. PARTICIPANTS: A total of 101 073 women who had no prior history of DM and who reported their usual menstrual cycle pattern at age 18 to 22 years on the baseline (1989) questionnaire. MAIN OUTCOME MEASURE: Incident reports of DM, with follow-up through 1997, compared among women categorized by menstrual cycle length (5 categories). RESULTS: During 564 333 person-years of follow-up, there were 507 cases of type 2 DM. Compared with women with a usual cycle length of 26 to 31 days (referent category) at age 18 to 22 years, the relative risk (RR) of type 2 DM among women with a menstrual cycle length that was 40 days or more or was too irregular to estimate was 2.08 (95% confidence interval [CI], 1.62-2.66), adjusting for body mass index at age 18 years and several other potential confounding variables. The RR of type 2 DM associated with long or highly irregular menstrual cycles was greater in obese women, but was also increased in nonobese women (at body mass indexes at age 18 years of <25, 25-29, and >/=30 kg/m, RRs were 1.67 [95% CI, 1.14-2.45], 1.74 [95% CI, 1.07-2.82], and 3.86 [95% CI, 2.33-6.38], respectively). CONCLUSION: Women with long or highly irregular menstrual cycles have a significantly increased risk for developing type 2 DM that is not completely explained by obesity.

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BackgroundInfluential
Comparison of metformin and thiazolidinediones in the management of polycystic ovary syndrome
Baillargeon, J., Iuorno, M. J., & Nestler, J. E. (2002) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-200208000-00003 · Cited by 14
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“Several studies assessed the link between menstrual cycle irregularities and cardiometabolic disease risk.(5,10,20,21) How-”
Influential
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Soria‐Contreras, D. C., Perng, W., Rifas‐Shiman, S. L., Hivert, M., Chavarro, J. E., & Oken, E. (2022) · Paediatric and Perinatal Epidemiology · doi:10.1111/ppe.12866 · Cited by 13
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Background
Ambulatory medical services utilization for menstrual disorders among female personnel of different medical professions in Taiwan: a nationwide retrospective cohort study
Koo, M., Chen, C.-H., Tsai, K.-W., Lu, M., & Lin, S. (2015) · BMC Women s Health · doi:10.1186/s12905-015-0220-3 · Cited by 13
“Furthermore, menstrual cycle irregularity before middle age had been shown to increase the risk of cardiovascular disease [5], type 2 diabetes [6], and osteoporosis [7].”
Background
Urinary Phytoestrogens and Relationship to Menstrual Cycle Length and Variability Among Healthy, Eumenorrheic Women
Levine, L. D., Kim, K., Purdue‐Smithe, A., Sundaram, R., Schisterman, E. F., Connell, M. T., DeVilbiss, E. A., Alkhalaf, Z., Radoc, J. G., Louis, G. M. B., et al. (2019) · Journal of the Endocrine Society · doi:10.1210/jendso/bvz003 · Cited by 13
“Menstrual irregularity has previously been associated with a variety of negative health outcomes, including increased risk for type 2 diabetes mellitus [34] and coronary heart disease [35].”
Background
Review: PCOS, insulin resistance and long-term risks for diabetes and vascular disease
Sattar, N. A. (2009) · The British Journal of Diabetes · doi:10.1177/1474651408101369 · Cited by 13
Abnormal bleeding patterns associated with menorrhagia in women in the community and in women presenting to primary care
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“Prolonged period 106 (14) 38 (28) Intermenstrual bleeding or postcoital bleeding 139 ( 19 ) 49 (36) Short cycle, intermenstrual bleeding or postcoital bleeding 301 (41) 93 (67) Short cycle, intermenstrual bleeding, postcoital bleeding or prolonged period 340 (46) 101 (73)”
Background
Insulin sensitivity and premenstrual syndrome
Trout, K. K., & Teff, K. L. (2004) · Current Diabetes Reports · doi:10.1007/s11892-004-0079-4 · Cited by 14
“It is of interest to note that women with diabetes have a higher prevalence of menstrual cycle disorders in general [13, 14 ].”
Background
Androgens, Irregular Menses, and Risk of Diabetes and Coronary Artery Calcification in the Diabetes Prevention Program
Kim, C., Aroda, V. R., Goldberg, R. B., Younes, N., Edelstein, S. L., Carrion-Petersen, M. L., Ehrmann, D. A., & Diabetes Prevention Program Outcomes Study Group (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01829 · Cited by 12
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[Retracted] Sleep Status and Menstrual Problems among Chinese Young Females
He, H. J., Yu, X., Chen, T., YANG, F. B., Zhang, M., & Ge, H. (2021) · BioMed Research International · doi:10.1155/2021/1549712 · Cited by 10
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Polycystic Ovarian Syndrome
Legro, R. S. (2004) · Elsevier eBooks · doi:10.1016/b978-012444562-8/50030-6 · Cited by 9
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“Our findings of a pro-atherogenic association of low SHBG and menstrual delay in adolescence with increasing ApoB/ApoA1 foretell outcomes in adult women, where women with a history of irregular cycles have increased risk of coronary heart disease (CHD) and type 2 diabetes mellitus compared to women with regular cycles…”
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Interactions of insulin and estrogen in the regulation of cell proliferation and carcinogenesis
Suba, Z., & Kásler, M. (2012) · Orvosi Hetilap · doi:10.1556/oh.2012.29287 · Cited by 8
Gut Hormones, Obesity, Polycystic Ovarian Syndrome, Malignancy, and Lipodystrophy Syndromes
Bloomgarden, Z. T. (2007) · Diabetes Care · doi:10.2337/dc07-zb07 · Cited by 8
“5% had type 2 diabetes (37), and in the Nurses’ Health Study, the rate of conversion to type 2 diabetes doubled in oligomenorrheic women, independent of weight (38).”
Background
The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women’s study
Appiah, D., Hedderson, M. M., Kim, C., Sidney, S. S., Sternfeld, B., Quesenberry, C. P., Wellons, M., & Gunderson, E. P. (2023) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2023.110593 · Cited by 7
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Polycystic Ovarian Syndrome, Biomarkers, and Metformin: Research, Risk, and Reality
Sattar, N. A., & Nelson, S. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2486 · Cited by 7
“66), adjusting for BMI at age 18 yr and several other potential confounding variables (17).”
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Shifts in Color Discrimination during Early Pregnancy
Orbán, L. L., & Dastur, F. N. (2012) · Evolutionary Psychology · doi:10.1177/147470491201000206 · Cited by 7
Polycystic Ovary Syndrome
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The Association between Menstrual Irregularities and the Risk of Diabetes in Premenopausal and Postmenopausal Women: A Cross-Sectional Study of a Nationally Representative Sample
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“In previous reports [12,13,15,16,22,23], the association between menstrual irregularities and diabetes appeared inconsistent depending on the age and menopausal status of the sample group.”
BackgroundResult
Diabetes Issues in Women and Children
Bloomgarden, Z. T. (2003) · Diabetes Care · doi:10.2337/diacare.26.8.2457 · Cited by 6
Associations of chronotype and insomnia with menstrual problems in newly employed nurses at university hospitals in the Republic of Korea
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“17 Furthermore, menstrual cycle changes increase the risk of severe health problems, such as breast cancer, 18 type 2 diabetes, 19 cardiovascular disease, 20 and premature mortality.”
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Contributions of white adipose tissue to energy requirements for female reproduction
Anaya, E. S., de Groot, E. L., Lydon, J. P., Pangas, S. A., & Hartig, S. M. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.04.012 · Cited by 7
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“20,21 However, emerging evidence suggests that even among women with PCOS, the subset with polymenorrhoea exhibits milder glucose impairment and lower levels of insulin resistance compared to those with oligome-norrhoea.”
Background
Herzinsuffizienz – geschlechtsspezifische Aspekte?
Regitz‐Zagrosek, V., Lehmkuhl, E., & Lehmkuhl, H. B. (2008) · Der Internist · doi:10.1007/s00108-008-2053-8 · Cited by 6
Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) risk
Issat, T., Nowicka, M., & Jakimiuk, A. J. (2015) · Ginekologia Polska · doi:10.17772/gp/2429 · Cited by 6
Comparative treatment between sitagliptin vs. metformin, alone or in combination, in patients with polycystic ovary syndrome. A clinical entity at high risk for developing diabetes mellitus and gestational diabetes: A pilot study
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“However, they have no effect on beta cell activity and therefore on progression to DM2 or gestational diabetes.(18,19) Incretins and DPP-4 inhibitors have been shown to enhance pancreatic -cell activity, inhibit apoptosis, and promote weight loss because of their anorectic effect, thus providing adequate weight contro…”
Background
Resistência insulínica e perfil metabólico em pacientes com síndrome dos ovários policísticos de peso normal e sobrepeso/obesidade
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“Large well-established, observational studies have shown an association between irregular menstrual cycles (MCs) and outcomes of type 2 diabetes mellitus [1] and coronary heart disease [2,3], citing polycystic ovary syndrome (PCOS) as the most likely pathway.”
Background
CONTROVERSIES IN ENDOCRINOLOGY : A MODERN MEDICAL QUANDARY: POLYCYSTIC OVARY SYNDROME, INSULIN RESISTANCE AND ORAL CONTRACEPTIVE PILLS
Diamanti‐Kandarakis, E., Baillargeon, J., & Jurno, M. J. (2003) · Cited by 6
Die Insulinresistenz beim polyzystischen Ovar-Syndrom
Schröder, A. K., Tauchert, S., Ortmann, O., Diedrich, K., & Weiss, J. M. (2003) · Wiener klinische Wochenschrift · doi:10.1007/bf03041041 · Cited by 6
Physical Activity and Menstrual Health Symptoms and Characteristics: A Systematic Review and Meta-Analysis of Observational Studies
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Chu, A. H. Y., Aris, I. M., Ng, S., Loy, S. L., Bernard, J. Y., Tint, M. T., Yuan, W. L., Godfrey, K. M., Chan, J. K. Y., Shek, L. P., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-66147-x · Cited by 5
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Bruinvels, G., & Pedlar, C. R. (2023) · Springer eBooks · doi:10.1007/978-3-031-21881-1_13 · Cited by 5
Conservative Management of Gynecologic Diseases
Diamanti‐Kandarakis, E., & KANDARAKIS, H. A. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1290.035 · Cited by 5
Evaluation of the Association between Menstrual Cycle Irregularity and Dental Pain or Chewing Discomfort in Women before Menopause
Song, I., Ki, E. Y., Han, K., Ryu, J., & Park, J. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8040454 · Cited by 5
“Women with long (a usual cycle length of 40 days or more) or highly irregular menstrual cycles have a significantly increased risk for developing type 2 diabetes mellitus [4], and the prevalence of type 2 diabetes is higher among women with a history of menstrual irregularity [5].”
Background
Role of hormonal risk factors in oral cancer development
Suba, Z., Maksa, G., Mihályi, S., & Takács, D. (2009) · Orvosi Hetilap · doi:10.1556/oh.2009.28595 · Cited by 5
Adolescent Obesity: Identifying A New Group of At-Risk Youth
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Angiotensin Receptor Blockers: Cardiovascular Protection in the Metabolic Syndrome
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Should patients with polycystic ovarian syndrome be treated with metformin
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Prevalence and Predictors of Impaired Glucose Tolerance and Diabetes Mellitus Type 2 in Patients with Polycystic Ovary Syndrome
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“The risk for dysglycemia is the highest among PCOS patients with both anovulation and hyperandrogenism, amplified by obesity, or the classic NIH phenotype [15].”
Background
CAUSES OF DYSFUNCTIONAL UTERINE BLEEDING IN PRE-MENOPAUSAL, PERI-MENOPAUSAL AND POST-MENOPAUSAL WOMEN; A SYSTEMATIC REVIEW OF WORLD LITERATURE BETWEEN YEAR 1992 TO 2017
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Hippocampal volume and affect in response to fluctuating estrogens in menstrual cycle irregularity: a longitudinal single-subject study
Heller, C., Güllmar, D., Koeppel, C. J., Rojczyk, P., Stein, H., Taylor, C. M., Jacobs, E. G., Derntl, B., Kikinis, Z., Walter, M., et al. (2024) · npj Women s Health · doi:10.1038/s44294-024-00023-1 · Cited by 6
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ResultInfluential
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Authors: Solomon, C. G.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Solomon, Caren G.
ORCID: Solomon, Caren G.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2001-11-21
Volume: 286
Issue: 19
Pages: 2421
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.286.19.2421
OpenAlex: W2043815784
Cited by: 362
References: 31
Citations by year: 2026: 5 · 2025: 4 · 2024: 11 · 2023: 15 · 2022: 25 · 2021: 23 · 2020: 12 · 2019: 6 · 2018: 15 · 2017: 15 · 2016: 13 · 2015: 14 · 2014: 9 · 2013: 15 · 2012: 23
FWCI: 17.24
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA50385, R01CA050385)
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: type 2 diabetes, menstrual cycle length, oligomenorrhea, menstrual irregularity, diabetes risk, obesity, insulin resistance, impaired glucose tolerance, women's health, Nurses' Health Study II
MeSH terms: Adult, Diabetes Mellitus, Type 2, Female, Humans, Menstrual Cycle, Obesity, Oligomenorrhea, Prospective Studies, Regression Analysis, Risk Factors, Body Mass Index

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Long or Highly Irregular Menstrual Cycles as a Marker for Risk of Type 2 Diabetes Mellitus

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